There are nearly 5 million Americans with congestive heart failure (CHF) and approximately 550,000 new cases are diagnosed in the U.S. each year. Congestive heart failure affects people of all ages, from children and young adults to the middle-aged and the elderly (Roger, et al., 2012). It is very crucial to find new resource of cardiac muscle regeneration for CHF treatments. There are various theories about the origin of regenerating cardiac muscle cells. These include self-replication of pre-existing adult cardiac muscle cells (Senyo, et al., 2012; Eulalio, et al., 2012), differentiation of adult resident cardiac progenitor cells (Smart, et al., 2011; Bolli, et al., 2011), dedifferentiation and proliferation adult cardiac muscle cells (Beltrami, et al., 2003; Jopling, et al., 2010; Porrello, et al., 2011), and transdifferentiation of fibroblast cells into cardiac muscle cells (Song, et al., 2012; Qian, et al., 2012). However, it remains controversial whether or not cardiomyocyte regeneration can be sufficient to reverse established cardiomyopathy.
Glucagon-like peptide-1 (GLP-1) is synthesized in intestinal endocrine cells in 2 principal major molecular forms, GLP-1 (7-36) amide and GLP-1(7-37) amide, which have wide bioactivities on CNS satiety centers, gastrointestinal motility, islet function and β cell growth, and energy homeostasis (Drucker, et al., 2001; Drucker, et al., 2002). Recently GLP-1 was found to have cardioprotective effects independent of those attributable to tight glycemic control (Halbirk, et al., 2010; Timmers, et al., 2009). Intravenous infusions of GLP-1 protein to patients with myocardial infarction or chronic heart failure improved global LV function and the function of ischemic LV segments. So far it has been only known that GLP-1 indirectly acts on GLP-1 receptors distributed on the membrane of cardiomyocytes and GLP-1R signaling to cAMP generation produces distinct downstream signaling events in intracellular calcium or ERK1/2 activation (Ussher, et al., 2012). However, no data have been published regarding the effects of GLP-1 gene delivery to heart.
The present disclosure satisfies a long-felt need in the art to provide therapy for one or more cardiac-related medical conditions, including to provide therapy for myocardial regeneration and reversal of heart failure, for example.